Mirtazapine is a useful antidepressant compound, and it can be synthesized by cyclization of 2-(4-methyl-2-phenylpiperazin-1-yl)pyridine-3-methanol with concentrated sulfuric acid. Known methods for isolating mirtazapine include a method in which the cyclized reaction mixture is diluted with water and then alkalinized, and the produced precipitate is separated and then extracted with methylene chloride and concentrated to obtain crude mirtazapine (Patent document 1); a method in which the cyclized reaction mixture is diluted with water and then alkalinized and extracted in the presence of toluene, concentrated, and crystallized in a toluene-heptane system (Patent document 2); and a method in which the cyclized reaction mixture is diluted with water and then alkalinized, the produced precipitate is separated, the mother liquor is concentrated and both of the obtained residues are combined and suspended in isopropanol, after which extraction and concentration are performed to obtain crude mirtazapine (see Patent document 1).
[Patent document 1] Japanese Patent Public Inspection No. 2004-500324
[Patent document 2] International Patent Publication No. WO 01/038330